Methods and apparatuses for analysing fluid samples

ABSTRACT

A method and apparatus for analyzing a fluid sample that includes loading the sample in a sample space in a sensor with an input and an output, applying an electromagnetic input signal to the input, measuring at the output a response signal that includes an output signal produced by the sensor while the sensor is contacted by the sample and the electromagnetic input signal is applied to the input, comparing the response signal against the electromagnetic input signal to generate a comparison, and matching the comparison against a set of comparisons for known substances.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a division patent application of co-pending U.S. patentapplication Ser. No. 14/438,022, filed Apr. 23, 2015, which claims thebenefit of International Application No. PCT/GB2013/000450 filed Oct.22, 2013, having a claim of priority to GB patent application number1219029.4, filed Oct. 23, 2012. The contents of these prior applicationsare incorporated herein by reference.

BACKGROUND OF THE INVENTION

This invention relates to sensing using electromagnetic waves, inparticular, but not exclusively, microwaves, for rapid analysis ofsubstances produced by or during a reaction or other procedure, forexample.

GB2203553 discloses a gas sensor having a layer of semiconductingorganic polymer such as a polypyrrole that can be exposed to a gas to bedetected. An alternating electric signal of varying frequency is appliedto conductors bridged by the polymer and the change in impedancecharacteristic of the sensor when exposed to the gas detected by animpedance analyser. A sensor unit may comprise a number of such sensorsof different polymers reacting to different gases. The frequency rangeused is 1 MHz to 500 MHz.

Known as an ‘electronic nose’, the gas sensor can be trained using aneural net to recognize different sets of changes in impedance of anarray of sensors in response to different gases. GB2203553 suggests thatit may be possible to detect particular gases by investigating changesin the impedance characteristic localised at particular frequencies, butnotes that it is difficult to do this on account of noise, optinginstead for a comparison system in which differences in the variation ofimpedance characteristics as compared with a reference gas such asnitrogen are determined over a range of frequencies and in particular,not using frequencies above 500 MHz.

This is clearly complex and time consuming, and it would appear alsothat the impedance characteristics change with time, on a scale ofminutes. The method appears suitable only for gases or vapours, and,more particularly, gases or vapours that react with a semiconductingpolymer.

BRIEF DESCRIPTION OF THE INVENTION

The present invention provides a robust method and apparatus fordetecting or identifying fluids generally, whether they be gases,vapours, liquids or flowing solids, such as powders and to do so in amore convenient way that is not time-dependent.

The invention comprises a method for analysing a fluid sample comprisingloading the sample in a sample space in a sensor comprising an input andan output, applying an electromagnetic input signal to the input,measuring at the output a response signal comprising an output signalproduced by the sensor while the sensor is contacted by the sample andthe electromagnetic input signal is applied to the input, comparing theresponse signal against the electromagnetic input signal to generate acomparison, and matching the comparison against a set of comparisons forknown substances.

The signal may be a microwave signal and may be in the frequency range 1MHz to 300 GHz and particularly in the range 500 MHz to 300 GHz.

The output signal may be a reflected or transmitted input signal, andthe measurement may comprise a measurement of its power and/or phase.The sensor input may be connected as by one or more transmission linesto a microwave generator, and the output to an analyser such as a vectornetwork analyser or a spectrum analyser.

A useful technique involves sweeping the signal across a range offrequencies and detecting a resonance—a peak in the reflected ortransmitted signal output. Some samples may exhibit more than one peak,and can be identified by their spectra, in the same way that elementscan be identified by their optical spectra.

The invention also comprises an apparatus for analysing a fluid sample,the apparatus including a sensor that includes a sample space forreceiving a fluid sample, an input for applying an electromagnetic inputsignal to the sample, an output connected to the sample space, thecapability for measuring an output signal at the output produced by thesensor while the sensor is contacted by the fluid sample and theelectromagnetic input signal is applied to the input, and the capabilityof comparing the output signal against the electromagnetic input signal.

The signal input may be adapted for connection to a signal generator byone or more transmission lines such as coaxial cables, and the signaloutput may be similarly adapted for connection to an analyser.

The sensor may comprise:

an electrically insulating substrate:

an active conductor layer on the substrate comprising signal input andoutput electrodes; and

a sample space adapted to accept a fluid sample adjacent the activeconductor layer.

The substrate may be on a base conductor layer.

The sample space may have dimensions of the order of size of theelectromagnetic wavelength. A 300 GHz microwave has a wavelength of 1mm, and a sample space of, say, 5 mm square and one or two millimetersdeep will give a good response to microwave interrogation.

The active conductor layer may have intercalated or interdigitated inputand output electrodes, which may have square, circular, spiral orstellate configuration.

The sample area may be defined by a well holding a known amount of thefluid sample.

In addition, the conductor layer may be covered with a transducercoating,

The transducer coating may be selected or adapted to respond in knownmanner to electromagnetic waves when in contact with a sample so thatthe sensor transmits and/or reflects electromagnetic waves in a mannercharacteristic of the sample.

The frequency range may extend from 9 kHz to 300 GHz, and may comprisethe microwave range 300 MHz to 300 GHz or any part or parts of it.

The base conductor layer may be of the same material as the conductorlayer on the substrate, or of a different material, either comprisingany well-conducting metal such as gold, silver, copper, platinum/goldalloy or a conductive carbon-based material. The electrically insulatingsubstrate may comprise any printed circuit board material, aglass-reinforced epoxy material such as FR4, a glass reinforced PTFE,Duroid® high frequency circuit materials, glass, or alumina, and may berigid or flexible. The material may have dielectric properties thatinfluence electromagnetic signal decay.

The transducer coating may be selected from metal oxides, polymers,mixtures of oxide and polymer, polymers filled with nanoparticles forenhanced conductivity, and which may operate in the percolation regionor near to the percolation threshold. Phosphate and nitrogen bindingpolymeric hydrogels, as well as cadmium phthalocyanines, may be used.Biological coatings such as enzymes, proteins or even living organismssuch as E. coli 600 or Pseudomonas aeruginosa can also be used. Theselected transducer coating may be a stable, general-purpose coatingthat may survive multiple measurements or may, as particularly withliving organisms, be of limited utility, adapted for one or a smallnumber of sample materials and/or reacting with or becoming contaminatedby a sample.

Different fluid analytes in contact with the transducer coating willexhibit different responses to microwaves, for example different levelsof attenuation, different resonant frequencies, different reflection andtransmission characteristics and so forth. Analytes will exhibitdifferent responses when in contact with different transducer coatings.

The invention also comprises a method for analysing a sample byelectromagnetic waves in the frequency region extending from 9 kHz to300 GHz, comprising placing the sample in contact with a transducercoating and measuring a response to electromagnetic waves applied to thetransducer coating in the said frequency region. The response may be aresonance at a particular frequency or attenuation of transmitted orreflected radiation.

The response may be measured from a signal reflected back along atransmission line supplying an interrogating signal or from radiatedenergy picked up by an aerial.

A library of responses may be built up from a series of measurements ondifferent substances, using different transducer coatings, so thatsubstances giving particular responses may be identified. Interrogationmay be carried out at particular frequencies in the frequency range, orby a sweep across the range or a part or parts of it.

The applied electromagnetic signal may be controlled by the response,for example, in a feedback loop, to adjust the frequency, for example,to achieve resonance.

The method may be carried out as an element of process control or in acontinuous monitoring role, in which samples are introduced robotically.

Methods and apparatus for analysing samples in accordance with theinvention will now be described with reference to the accompanyingdrawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a section through one embodiment of sensor;

FIG. 2 is a plan view of the sensor of FIG. 1;

FIG. 3 is a view of one embodiment of a different electrodeconfiguration for the sensor of FIGS. 1 and 2;

FIG. 4 is a view of another embodiment of electrode configuration forthe sensor of FIGS. 1 and 2;

FIG. 5 is a diagrammatic illustration of a sensor connected in ameasuring system; and

FIG. 6 is a graphical display of power against frequency for particularsensor configurations with a particular analyte.

DETAILED DESCRIPTION OF THE INVENTION

The drawings illustrate apparatus for analysing a fluid sample providinga sample space 12 in a sensor 11 with input and output electrodes 14, 15for an electromagnetic signal, and means for measuring an output signaland comparing it against an input signal, and matching the comparisonagainst a set of comparisons for known substances.

The sensor 11 comprises:

an electrically insulating substrate 16:

an active conductor layer 13 on the substrate comprising the signalinput and output electrodes 14, 15; and

a well defining the sample space 12 adapted to accept a fluid sampleadjacent the active conductor layer 13.

The substrate 16 is on a base conductor layer 17.

The active conductor layer 13 is in the form of printed intercalatedfinger electrodes 14, 15 with contact pads 14 a, 15 a constituting anexternal connector arrangement. The active conductor layer 13 may be ofgold, copper, silver, platinum/gold alloy, conductive carbon material orindeed any of the usual conductor materials, as may the base layer 17,which may be of the same conductor material as the layer 13, ordifferent. The electrode pattern may comprise simple interdigitatedfingers as illustrated or more complex patterns such as stellate, asshown in FIG. 3, or circular, as shown in FIG. 4.

The active conductor layer 13 is covered with a transducer coating 18(not shown in FIG. 2 for illustrative purposes) selected or adapted torespond in known manner to electromagnetic waves in a desired operatingfrequency range when in contact with a sample so that the sensor 11transmits and/or reflects electromagnetic waves in a mannercharacteristic of the sample.

The transducer coating 18 is selected from metal oxides, polymers,mixtures of oxide and polymer, polymers filled with nanoparticles forenhanced conductivity, and which may operate in the percolation regionor near to the percolation threshold. Phosphate and nitrogen bindingpolymeric hydrogels, as well as cadmium phthalocyanines, may be used.

Biological coatings such as enzymes, proteins, even living organismssuch as E. coli 600 or Pseudomonas aeruginosa may be used.

The selected transducer coating 18 may be a stable, general-purposecoating that may survive multiple measurements or may be of limitedutility, adapted for one or a small number of sample materials and/orreacting with or becoming contaminated by a sample.

The transducer coating 18 may serve only to insulate the conductor layerfrom the sample, but may also influence the sensor response to thesignal, without necessarily reacting or interacting in any physical orchemical way with the sample.

The operating frequency range may extend from 9 kHz to 300 GHz, and maycomprise the microwave range 300 MHz to 300 GHz or any part or parts ofit. The size of the sample space is commensurate with the signalwavelength, and 300 GHz signal having a free-space wavelength of 1 mm,the sample space being typically a few millimeters, say five to tenmillimeters square and typically one or two millimeters deep, forexample, an area between 20 and 50 square millimeters with a volumebetween 20 and 100 cubic millimeters.

The electrically insulating substrate 16 comprises any printed circuitboard material, a glass-reinforced epoxy material such as FR4, a glassreinforced PTFE, Duroid® high frequency circuit materials, glass, oralumina, and may be rigid or flexible. The material may have dielectricproperties that influence electromagnetic signal decay.

FIG. 5 illustrates a sensor 11 in a measuring system comprising an EMgenerator 31 connected via a cable 32 or by radiating microwaves or bothand an analyser 33 connected by a cable 34 and/or radiating microwaves.The EM generator 31 comprises a tunable microwave generator having afrequency range of 9 kHz to 300 GHz, and the analyser 33 is adapted tomeasure power and/or phase in this frequency range transmitted throughthe sensor 11.

FIG. 6 is a graphical display showing transmitted power againstmicrowave frequency in a sweep from zero to 15 GHz for a sensor 11 inwhich the transducer coating 18 is hydroxyapatite and the analyte isisopropyl alcohol (IP A). Trace A is for the sensor without either thetransducer coating or the IPA, trace B is for the coating 18 without theIP A, trace C is for the sensor without the coating but with the IPA,and trace D is for the sensor with both transducer coating 18 and IPA.This latter trace D shows a marked resonance at 7.5 GHz.

Different fluid samples in contact with different transducer coatingswill exhibit different responses to microwaves, for example differentlevels of attenuation, different resonant frequencies, differentreflection and transmission characteristics and so forth. For anyparticular application, for detecting a particular analyte or one ormore of a number of possible analytes, there will be a suitable choiceof the transducer coating 18.

Sensors as described can be fashioned in different sizes andconfigurations using different materials to adapt them to identifyingand measuring properties of different substances. A sensor used toidentify and measure one class of substances, say oils, will be designedso as to be particularly responsive to substances of that class andoperated within a frequency range that includes resonant frequencies ofsuch substances. A library of responses to a frequency sweep forsubstances of that class can be built up and referred to for identifyingsuch substances when presented.

The sensors might be used in quality control, moreover, properties ofsamples from production being measured to test conformity from astandard.

The invention claimed is:
 1. A method for analysing a fluid sample, themethod comprising: loading the sample in a sample space in a sensorcomprising an input and an output; applying an electromagnetic inputsignal to the input; measuring at the output a response signalcomprising an output signal produced by the sensor while the sensor iscontacted by the sample and the electromagnetic input signal is appliedto the input; comparing the response signal against the electromagneticinput signal to generate a comparison; matching the comparison against aset of comparisons for known substances; and sweeping theelectromagnetic input signal across a range of frequencies and detectinga resonance, wherein the swept frequency range includes more than oneresonance.
 2. A method according to claim 1, further comprisingcontrolling the electromagnetic input signal in a feedback loop, toadjust the frequency.
 3. A method according to claim 1, furthercomprising controlling the electromagnetic input signal to achieveresonance.
 4. A method according to claim 1, carried out as an elementof process control or in a continuous monitoring role, in which samplesare introduced robotically.
 5. Apparatus for analysing a fluid sample,the apparatus including a sensor comprising: a sample space forreceiving a fluid sample; an input for applying an electromagnetic inputsignal to the sample; an output connected to the sample space;measurement means for measuring an output signal at the output producedby the sensor while the sensor is contacted by the fluid sample and theelectromagnetic input signal is applied to the input; means forcomparing the output signal against the electromagnetic input signal;and a microwave analyser connected to the output, wherein the microwaveanalyser is connected to receive a reflected input signal or atransmitted input signal.
 6. Apparatus according to claim 5, wherein thesample space has a volume between 20 and 100 cubic millimeters. 7.Apparatus according to claim 5, wherein the sample space has an areabetween 20 and 50 square millimeters.
 8. Apparatus according to claim 5,wherein the sensor further comprises: an electrically insulatingsubstrate; and an active conductor layer on the substrate comprisingsignal input and output electrodes of, respectively, the input andoutput of the sensor; wherein the sample space is adjacent the activeconductor layer.
 9. Apparatus according to claim 8, wherein thesubstrate is on a base conductor layer.
 10. Apparatus according to claim9, wherein the base conductor layer is of the same material as theactive conductor layer.
 11. Apparatus according to claim 9, wherein thebase conductor layer is of a different material from the activeconductor layer, either comprising any well-conducting metal such asgold, silver, copper, platinum/gold alloy or a conductive carbon-basedmaterial.
 12. Apparatus according to claim 8, wherein the input andoutput electrodes have intercalated or interdigitated patterning. 13.Apparatus according to claim 8, further comprising a transducer coatingcovering the conductor layer and adapted to respond in known manner toelectromagnetic waves when in contact with known substances so that thesensor transmits and/or reflects electromagnetic waves in a mannercharacteristic of the known substances.
 14. Apparatus according to claim13, in which the transducer coating is selected from metal oxides,polymers, mixtures of oxide and polymer, polymers filled withnanoparticles for enhanced conductivity.
 15. Apparatus according toclaim 13, in which the transducer coating comprises phosphate andnitrogen binding polymeric hydrogels or cadmium phthalocyanines. 16.Apparatus according to claim 13, in which the transducer coatingcomprises a biological material such as an enzyme or a protein, or aliving organism such as E. coli 600 or Pseudomonas aeruginosa. 17.Apparatus according to claim 13, in which the transducer coating is astable, general-purpose coating that will survive multiple measurements.18. Apparatus according to claim 13, in which the transducer coating isof limited utility, adapted for one or a small number of samplematerials and/or reacting with or becoming contaminated by a sample.